Cardiac- and respiration-driven vascular pulsations influence cerebrospinal fluid (CSF) oscillations and neurofluid dynamics and are considered relevant for perivascular fluid transport and brain homeostasis. In atrial fibrillation (AF), irregular cardiac rhythm alters cerebral hemodynamics and may affect CSF flow dynamics. This exploratory pre-post pilot study investigated physiological changes in CSF and blood flow dynamics following AF intervention. This pilot study included 7 patients with AF, using a 3 T MRI system. To capture CSF and blood flow, real-time phase-contrast flow MRI was employed in the aqueduct, the internal carotid artery, the jugular vein and the sagittal sinus. T1-weighted MRI and fast T1 mapping characterized the tissue anatomy and integrity and EPI diffusion assessed fluid motion along the perivascular space. Artefact-free STEAM diffusion described whole-brain CSF dynamics. Physiological data were recorded simultaneously during MRI. Before intervention, AF patients exhibited reduced CSF flow and irregular CSF oscillatory patterns. After intervention, CSF dynamics shifted toward more periodic, cardiac-dominated oscillatory patterns, with increased CSF flow volume, consistent with altered neurofluid dynamics following restoration of sinus rhythm. Blood flow in the internal carotid artery, jugular vein, and sagittal sinus similarly shifted toward sinus rhythmic patterns, while DTI-ALPS, quantitative T1 measures, brain volume, ventricular size, and white matter integrity remained unchanged. Within-subject comparisons indicated that restoration of sinus rhythm was accompanied by measurable alterations in CSF and blood flow dynamics.
The brain coordinates behavior across timescales spanning milliseconds to days through cross-frequency coupling (CFC)-the mechanism by which slow oscillations modulate the amplitude and timing of faster oscillations, creating a hierarchical temporal architecture. Existing frameworks have typically addressed oscillations within narrow frequency ranges, leaving cross-timescale coordination mechanisms underspecified. I propose a unified framework termed Temporal-Oscillatory Entrainment (TOE), which organizes entrainment phenomena (using the term in its chronobiological sense) across nine frequency ranges into three functional categories: neural (high gamma through delta), biological (behavioral through circadian), and social (weeks and longer). The framework identifies the auditory-motor system as a privileged pathway, given that CFC occurs in the auditory brainstem and rate-restricted coupling at approximately 4-5 Hz reflects an intrinsic auditory-motor rhythm. Musical training studies demonstrate that rhythmic experience induces neuroplastic changes spanning subcortical to cortical levels, with transfer effects documented across multiple frequency bands-from millisecond-level discrimination to phrase-level processing. Beyond neural timescales, respiratory rhythms provide a well-characterized example of behavioral-frequency oscillations coupling to neural activity, while social rhythm therapy research demonstrates that stabilizing daily behavioral patterns affects circadian function and mood regulation. Musical ensemble coordination instantiates the same hierarchical nesting and phase-based coupling that characterizes neural CFC. The TOE framework generates testable predictions about bidirectional transfer effects between timescales, individual differences in entrainment capacity, and the distinct contributions of solo versus ensemble musical experience, with implications for understanding cognitive development, clinical intervention, and the neurobiological foundations of temporal coordination.
20% of Americans are at risk for environmental circadian rhythm disruptions (CRD) due to shift work, leading to substantial negative health outcomes. However, females are especially affected with greater vulnerability for substance use (SU) and adverse outcomes associated with pregnancy, including for offspring at birth and later in life. In mice, prenatal CRD (pCRD) recapitulates these risks, but it is unknown whether pCRD affects SU in mature offspring. To investigate this, C57BL/6J dams were disrupted by reversing the light/dark cycle during gestation. Following pCRD, reward- (cocaine conditioned place preference, intravenous self-administration) and mood-related behaviors (open field, elevated plus maze, light/dark box, forced swim) were measured in adult offspring. Adult female offspring of dams exposed to CRD developed an anhedonic-like phenotype with decreased food self-administration, cocaine intake and reinforcing properties of cocaine. Opposingly, pCRD male offspring showed a SU-like phenotype with increased cocaine preference, higher order food self-administration and cocaine reinforcement. Interestingly, these divergent behavioral outcomes were not specific to reward. While female pCRD mice showed increased anxiety-like behavior, pCRD males showed decreased anxiety/increased risk-taking behavior, as well as decreased immobility in the forced swim test. Rhythms in corticosterone were also sex-specifically affected by pCRD. These results suggest that pCRD may predispose individuals to distinct psychiatric disorders based on sex with mood disorders developing in females and SU disorders developing in males. By better understanding how disrupted rhythms during pregnancy affect behavior in adulthood, we can develop novel therapeutic approaches for SU and mood disorders in adults.
Whether de novo organized left atrial tachyarrhythmia (LAT) shows preserved left atrial appendage (LAA) mechanics has not been adequately characterized. We compared LAA peak emptying velocity across atrial fibrillation (AF) phenotypes and de novo LAT. Multicenter retrospective cohort of 634 consecutive first-ablation candidates undergoing pre-ablation transesophageal echocardiography (TEE) at five centers: paroxysmal AF (PAF, n = 146), persistent AF (PeAF, n = 310), long-standing persistent AF (LsPeAF, n = 86), and LAT (n = 92). Markedly reduced LAA function was peak emptying velocity <25 cm/s. Multivariable regression adjusted for rhythm during TEE, CHA2DS2-VASc, body mass index (BMI), left ventricular ejection fraction (LVEF), and left atrial (LA) diameter. Mean LAA velocity was 55.7 ± 19.4 (PAF), 44.3 ± 18.5 (PeAF), 31.0 ± 12.5 (LsPeAF), and 36.6 ± 13.5 cm/s (LAT); p < 0.001. LAT lay closer to LsPeAF than to PAF and did not differ from LsPeAF (Tukey p = 0.140). Prevalence of velocity <25 cm/s: 2.7%, 11.9%, 32.6% and 18.5% (p < 0.001). After adjustment, larger LA diameter (β = -0.53/mm, p < 0.001) and higher CHA2DS2-VASc (β = -1.93/point, p < 0.001) were independently associated with lower velocity. Compared with LAT, PAF had lower odds of velocity <25 cm/s (OR 0.19, 95% CI 0.06-0.62). De novo organized LAT exhibits LAA mechanical dysfunction comparable to long-standing persistent AF rather than to PAF. Organized rhythm does not imply preserved appendage function. LAA peak emptying velocity may serve as a functional remodeling marker for pre-ablation phenotyping.
In this Perspective, we suggest combining physiological, neurobiological, behavioural, and social data from multiple marine mammal species to create evolutionary models of the emergence of social vocal coordination. Marine mammal sound production mechanisms have evolved to manage vocalizing and breathing in an aquatic environment, potentially releasing functional constraints on the control of vocal timing. Intervals in rhythmic cetacean vocalizations cover a remarkable temporal range, from less than a millisecond in porpoise burst pulses to 10 s in sperm whale slow clicks. Many cetaceans demonstrate temporally coordinated social behaviour, while pinnipeds express high variability in vocal plasticity and social behaviour. The systematic variability of vocal production mechanisms, vocal rhythms, and sociality can be compared phylogenetically to generate models for the evolution of social rhythm in the vocal domain.
Single-component cosinor models are commonly used to assess circadian dysregulation in 24 h ambulatory blood pressure (BP) measurements, but they cannot capture more complex or asymmetric circadian patterns. This study evaluated 4 mixed-effects cosinor models by applying them to systolic and diastolic blood pressure (SBP and DBP) data collected from children with obstructive sleep apnea (OSA) and healthy controls (non-OSA) and compared the estimated circadian parameters between groups. The analysis included 24-h BP monitoring data from 219 age- and gender-matched children (117 controls, 52 with mild OSA, and 50 with moderate-to-severe OSA [MS-OSA]). Mixed-effects cosinor models with 1 to 4 components estimated various circadian parameters: acrophase, amplitude, and time arrived at peak velocity (TAPV). The 3-component mixed-effects cosinor model provided the best fit for SBP and DBP data. The estimated MESOR (midline estimating statistic of rhythm) was 106 mmHg for SBP and 64 mmHg for DBP in the control group; the MS-OSA group had a higher DBP MESOR (66 mmHg). Children with OSA had a dampened early afternoon BP peak and an increased late-evening BP peak. The timing differences for the first BP peak were more pronounced in the morning for SBP, and from morning to mid-day for DBP, particularly in MS-OSA. TAPV occurred in the morning in all models, with slight timing differences in SBP for mild OSA, and in DBP for MS-OSA, compared to controls. Although single-component cosinor models are traditionally used for 24-h BP rhythms, the multi-component mixed-effects models provided a better fit and captured disease-related differences.
The circadian rhythm is an intrinsic timekeeping system that precisely regulates a wide range of physiological and pathological processes. Its core molecular mechanisms and regulatory networks are gaining increasing attention in the field of lung cancer research. Substantial evidence indicates that circadian clock genes are not only deeply involved in lung cancer initiation and progression but also profoundly influence the dynamic remodeling of the tumor immune microenvironment (TIME) in lung cancer. This review summarizes the expression patterns and functional mechanisms of circadian clock genes in various cancers. It specifically elaborates on their regulatory roles in immune cell function, malignant behaviors of tumor cells, and interactions with stromal cells. The review also details how circadian disruption drives lung cancer development, progression, and immune evasion. Besides, we explore the potential impact of heterogeneity in circadian gene expression on the efficacy of immune checkpoint inhibitors (ICIs) in lung cancer, synthesize current knowledge on how circadian rhythms influence clinical responses to and adverse effects of immunotherapy in lung cancer, and highlight the translational potential of chronotherapy-optimizing drug administration timing based on circadian principles-to enhance therapeutic outcomes and reduce toxicity. By integrating recent preclinical and clinical evidence, this review provides a theoretical foundation for circadian-based precision immunotherapy in lung cancer and outlines future directions for innovative therapeutic strategies targeting the circadian machinery.
Recent work shows that the brain's arousal system remains active during sleep, with rhythmic locus coeruleus (LC) activity shaping sleep architecture and supporting memory consolidation. The LC releases norepinephrine (NE) in infraslow (∼0.02 Hz) bouts that gate NREM sleep spindles. Here, we demonstrate that heart rate (HR) fluctuations during NREM are tightly phase-locked to these NE rhythms, identifying the LC as a key driver of very-low-frequency HR variability (VLF-HRV), an understudied autonomic signal. Using optogenetics, transient LC inhibition blunts HR slowing, whereas LC activation produces rapid HR acceleration, directly linking LC output to cardiac control during sleep. We further show that infraslow HR variability is a cross-species marker of spindle-dependent memory processing. In mice, the amplitude of HR decelerations during NREM correlate with spindle activity and subsequent memory performance. Remarkably, human sleepers show the same pattern: stronger VLF-HR fluctuations during NREM correspond to increased spindle expression and better overnight memory retention. These findings reveal a mechanistic pathway through which LC activity modulates autonomic physiology during sleep and identify infraslow HR variability as a non-invasive marker of brainstem function and memory-promoting sleep. Because LC degeneration occurs early in neurodegenerative disease, sleep-derived HR metrics may provide a scalable indicator of emerging neuromodulatory dysfunction.
Circadian rhythm sleep disorders (CRSD) may disrupt neurovascular regulation and increase open-angle glaucoma (OAG) and ocular hypertension (OHT) risk. This study assessed associations with OAG, primary open-angle glaucoma (POAG), and OHT and examined melatonin's modifying effect. A retrospective cohort study using TriNetX data included adults (≥ 18 years) with CRSD matched 1:1 to polysomnography-tested controls without sleep disorders. Melatonin subgroups were analyzed. Among 24,730 matched pairs, ICD-10-defined OAG, POAG, and OHT at 1, 3, and 5 years were assessed using adjusted hazard ratios (aHRs) and Kaplan-Meier analyses. After matching, 24,730 patients were included in each group. The CRSD group had a significantly higher risk of OAG at 1 year (0.14% vs. 0.04%; P=.0005; aHR 2.67, 95% CI 1.42-5.02), 3 years (0.25% vs. 0.07%; P < .0001; aHR 3.02, 95% CI 1.81-5.05), and 5 years (0.27% vs. 0.08%; P < .0001; aHR 2.88, 95% CI 1.78-4.66). Similar trends were observed for POAG, while no significant differences were seen for OHT. Among CRSD patients not using melatonin (n = 24,150 pairs), OAG risk remained significantly elevated at all time points. In contrast, among melatonin users (n = 4,081 pairs), the risks of OAG, and OHT were not significantly different from controls (5-year OAG: 0.52% vs. 0.32%; P = .23; aHR 2.07, 95% CI 0.88-4.84). CRSD is associated with an increased risk of OAG and POAG, in patients not using melatonin. Melatonin use appears to decrease this risk, suggesting a potential protective effect.
Social interaction involves coordination between individuals across multiple domains, including neural activity, behaviour and physiology. An increasing number of studies shows that interpersonal coordination and synchrony can be detected in each of these modalities, but the functional significance of these different types of coordination remains unclear. This paper examines the challenge of understanding coordination in terms of the timescales of interaction. We provide a novel mapping of interaction types and measurement methods across timescales spanning from milliseconds to minutes. We review candidate mechanisms of synchrony and coordination in both neural systems and behaviour, and consider how these measures relate to real world outcomes such as learning and development. Overall, we provide an integrative approach that, by taking timescales into account, aims to offer a better understanding of the origins and interpretation of interpersonal coordination.
A growing body of literature has illustrated the importance of understanding the circadian clock due to its connection to a wide array of molecular and physiological processes. Numerous methods have been developed in order to monitor the status of the circadian clock in living tissue; however, most methods are either costly or labor intensive, and often require precise conditions that lowers throughput and limits flexibility in the size, age, or type of plant to be assayed. Here, we present an affordable and adaptable methodology for assaying circadian period using the well-characterized circadian output of leaf movement. Employing fully automated time-lapse photography using Raspberry Pi cameras and predominantly automated image post-processing, this methodology minimizes manual input to expedite circadian analysis, thus improving throughput. Additionally, the top-down setup used in this method is appropriate for a wide range of sizes and ages of plants, allowing for an expansion of the scientific questions that can be assayed by this methodology.
Intramyocardial injection of hiPSC-CMs is a promising cell replacement therapy for myocardial infarction, but EAs after transplantation hinder their clinical translation. This study aims to analyze the characteristics of EAs after hiPSC-CMs transplantation, and to identify risk factors associated with the occurrence of EAs. This study included patients undergoing CABG combined with hiPSC-CMs transplantation (experimental group) or isolated CABG (control group) at our hospital between November 2023 and November 2025. Patients in the experimental group were assigned to low- and high-dose groups (0.5×108 and 1.5×108 cells). EA characteristics were analyzed and compared between the two subgroups. Univariate logistic regression was performed to identify risk factors for EAs. A total of 24 patients in the experimental group were enrolled, 13 (54.2%) of whom developed EAs originating from the cell injection site (localized by ECG QRS morphology). Initially, EAs were paroxysmal (heart rate: 55-96 bpm, 72.15±9.77 bpm), progressing to sustained episodes over hours with increased heart rate (max 111-185 bpm, 146.00±21.02 bpm) and R-R interval variability. No hemodynamic abnormalities were detected in any patient during EA episodes. Atrial pacing, and electrical cardioversion reduced EA rate but failed to terminate EAs. EA incidence was significantly higher in the high-dose than low-dose group (10/12 [83.3%] vs 3/12 [25.0%], P=0.012). Univariate logistic regression showed hiPSC-CM dose was significantly associated with EA occurrence (OR=15.00, 95%CI: 2.02-111.17, P=0.008). The occurrence of EAs was likely driven by an automaticity mechanism, and hiPSC-CMs transplantation dose was significantly correlated with EA incidence.
Liver metabolism is under tight control of the circadian system. Disruption of key clock gene expression (desynchronosis) leads to the misalignment of metabolic pathways. However, the relationship between circadian dysregulation and hepatic protein-synthetic function, as well as its sexual dimorphism, remains poorly understood. To evaluate the effect of chronic photoperiod disruption on hepatic protein-synthetic function (total protein, albumin) and to establish its relationship with the expression of key circadian proteins (BMAL1, CLOCK, PER2) in male and female rats, as well as to assess the efficacy of exogenous melatonin in correcting the identified disturbances. The study was performed on 240 adult Wistar rats (120 males, 120 females). Animals were divided into 3 groups: control (light: dark 10:14 h), dark deprivation (LL, constant light for 21 days), and LL + melatonin (12 mg/L drinking water). Plasma levels of total protein and albumin were measured. Immunohistochemistry was used to assess the percentage of positively stained hepatocytes for BMAL1, CLOCK, and PER2. Statistical analysis included two-way ANOVA, Pearson correlation analysis, ANCOVA, and ROC analysis. Dark deprivation reduced albumin levels by 15.7% in males and by 15.9% in females compared to controls. Two-way ANOVA revealed significant effects of "lighting conditions" (F = 145.3, p < 0.0001), "sex" (F = 18.7, p < 0.01), and their interaction (F = 7.2, p < 0.05). BMAL1 and CLOCK expression decreased by more than 70% in both sexes, whereas PER2 expression paradoxically increased by 28.9-35.0%. Strong correlations were found between albumin levels and expression of BMAL1 (r = 0.79-0.81, p < 0.001), CLOCK (r = 0.69-0.74, p < 0.001), and PER2 (r= - 0.68 to - 0.71, p < 0.001). ANCOVA (R²=0.71, p < 0.0001) identified BMAL1 expression as the most significant independent predictor of albumin levels (β = 0.52, p < 0.0001), with sex retaining independent significance (p = 0.02). ROC analysis demonstrated high predictive performance of BMAL1 expression for hypoalbuminemia (AUC = 0.87-0.89, p < 0.0001). Melatonin treatment fully restored the expression of all examined circadian proteins and normalized protein synthetic parameters to control levels in both sexes. Chronic photoperiod disruption induces profound hepatic desynchronosis characterized by suppression of BMAL1/CLOCK and accumulation of PER2, which is associated with decreased protein synthetic function. A pronounced sexual dimorphism in susceptibility to desynchronosis was identified. BMAL1 expression is a highly informative predictor of hypoalbuminemia. Exogenous melatonin fully restores the impaired parameters, supporting its use as an effective chronobiotic. The liver works on a daily (circadian) rhythm. When this rhythm is disrupted—for example, by constant light exposure—it can harm liver function. However, scientists did not know exactly how rhythm disruption affects the liver’s ability to make proteins (like albumin), or whether males and females respond differently. This study tested whether constant light harms liver protein production, and whether the sleep hormone melatonin could fix it. They used 240 adult rats (120 males, 120 females). The rats were split into three groups:1. Normal light-dark cycle (control).2. Constant light for 21 days (to disrupt their body clock).3. Constant light plus melatonin in their drinking water.They measured blood levels of total protein and albumin (a key protein made by the liver). They also measured three key clock proteins (BMAL1, CLOCK, PER2) in the liver cells. Constant light lowered albumin levels by about 16% in both male and female rats. It also caused major changes in the liver’s clock proteins: BMAL1 and CLOCK dropped by over 70%, while PER2 increased. These changes were strongly linked to lower albumin levels. The study also found that sex mattered—males and females responded differently to rhythm disruption. Using a statistical model, BMAL1 was the best predictor of low albumin. Importantly, melatonin treatment fully restored all clock proteins and normalised protein production in both sexes. Disrupting the body’s daily rhythms harms the liver’s ability to make essential proteins. The clock protein BMAL1 may serve as a useful marker for liver problems. Melatonin—a natural hormone already used for sleep disorders—could potentially help protect liver function when circadian rhythms are disturbed (e.g., in shift workers, people with chronic jet lag, or those living under abnormal light cycles).
Pulmonary vein isolation (PVI) alone achieves modest arrhythmia freedom in persistent atrial fibrillation (PeAF). Cryoballoon ablation (CBA) offers a single-shot alternative to radiofrequency ablation (RFA) that streamlines procedural workflow. We aimed to quantify the clinical efficacy, procedural efficiency, and safety of CBA versus RFA through a meta-analysis of randomized controlled trials (RCTs). Systematic review of PubMed, Embase, and Scopus identified 5 RCTs enrolling 1,091 patients (515 CBA, 576 RFA). The primary endpoint was 12-month freedom from any atrial arrhythmia, with isolated AF, and atrial tachycardia/flutter evaluated as secondary endpoints. Random-effects models generated relative risks (RRs) and mean differences (MDs) with 95% confidence intervals (CI). Time-to-event data were pooled using a generic inverse-variance approach to derive hazard ratios (HR). CBA and RFA demonstrated equivalent freedom from any arrhythmia (RR 0.97, 95% CI 0.81-1.15; p = 0.71). Time-to-event analysis corroborated a comparable recurrence hazard (HR 0.91, 95% CI 0.67-1.24; p = 0.56; I2 = 0%). Repeat ablation rates were identical (RR 0.93; p = 0.50). CBA significantly reduced procedural time (MD -45.37 min; p < 0.0001), while major complications were comparable (1.5% vs. 2.7%; p = 0.18). Trial sequential analysis indicated that further randomization is unlikely to demonstrate superiority. In PeAF, CBA and RFA achieve equivalent 12-month arrhythmia-free survival and comparable repeat-ablation rates, while CBA confers a highly significant reduction in procedural time. However, reliance on 12-month follow-up and heterogeneous rhythm surveillance protocols may limit assessments of true long-term durability.
Pulmonary vein isolation (PVI) is an established treatment for symptomatic atrial fibrillation (AF). To date, cryoballoon (CB) ablation has been the most widely adopted single-shot approach, while pulsed field ablation (PFA) has emerged as a non-thermal alternative designed to preferentially ablate myocardial tissue and reduce collateral injury. PulseSelect™ is a CE-marked and FDA approved PFA system specifically developed for PVI. We compared acute and one-year outcomes of PulseSelect PFA versus fourth-generation cryoballoon (CB4) ablation in routine clinical practice. This multicenter analysis included 254 consecutive patients undergoing first-time PVI in 10 Italian medium-volume centers between January 2024 and February 2025: 121 treated with PulseSelect and 133 with CB4. Baseline clinical and echocardiographic characteristics were prospectively collected. Procedural workflow, anesthesia strategy, procedure duration, fluoroscopy time, and periprocedural complications were assessed. Follow-up consisted of scheduled visits with rhythm monitoring, and arrhythmia recurrence was evaluated using Kaplan-Meier analysis. A total of 254 consecutive patients (mean age 62 ± 9 years, 28.3% women with paroxysmal AF in 76.4%) undergoing first-time PVI were included in the analysis: 133 treated with CB4 and 121 with PS PFA, with largely comparable baseline characteristics. General anesthesia was more frequently used with PulseSelect than with CB4 (74.4% vs. 16.5%). Mean skin-to-skin procedure duration was shorter with PulseSelect (62.4 ± 18 min) compared with CB4 (71.4 ± 30 min; p = 0.005), while fluoroscopy time was longer with PulseSelect. No acute complications occurred in the PulseSelect group; three transient phrenic nerve palsies were observed with CB4. At 12 months, no statistically significant difference in arrhythmia recurrence was observed between PulseSelect and CB4 (17.4% vs. 15.0%; p = 0.46). In this real-world multicenter cohort, PulseSelect PFA and CB4 ablation showed excellent acute safety and no statistically significant differences in one-year arrhythmia recurrence were observed between the two treatment strategies.
Light is a major environmental factor regulating circadian rhythms, sleep- wake cycles, and mood-related behaviors. Patients with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience circadian disruption and poor sleep quality, which severely compromise their quality of life; however, the relationship between light exposure and illness severity remains largely unknown. An observational cross-sectional cohort secondary study used collected data from 100 ME/CFS patients and 56 healthy controls to explore the impact of spontaneous light exposure on multidimensional health status and circulating biochemical parameters. Demographic and clinical features were assessed using validated patient-reported outcome measures. Light intensity, wrist temperature, and physical activity were continuously monitored at home over one week using wrist-worn actigraphy. Light intensity during predefined intervals and rhythmic variables of light cycle were calculated. Principal component analysis (PCA) was applied to reduce dimensionality of light variables. Multivariable analysis was performed adjusting for age, sex, body mass index, and physical activity. Following PCA of the light patterns, two components emerged across groups with high consistency: PC1 (explaining 61.7% of the total variance) reflected higher daytime light and rhythm stability, and PC2 (explaining 16.1%) represented nocturnal/early-morning light and rhythm instability. In ME/CFS patients, light variables were more extensively associated with clinical outcomes measures (FIS-40, PSQI and SF-36) than in healthy controls (all p < 0.05). Furthermore, PC2 was associated with higher levels of VCAM-1 and triglycerides, and lower serotonin concentrations (all p < 0.05). Four distinct light patterns were identified based on PCA scores: nocturnal light, healthy, adverse, and low diurnal light. ME/CFS patients exhibiting the healthy light pattern showed significantly lower fatigue, fewer sleep complaints, reduced autonomic dysfunction, and higher quality of life compared to those with the adverse light pattern (all p < 0.05). No significant differences were observed among healthy controls. Light exposure patterns show distinct associations with symptom variability in ME/CFS compared to healthy controls. More stable daytime light appears to relate to better symptom profiles, whereas irregular exposure and nocturnal light are linked to poorer health outcomes. Although causality cannot be inferred, these findings highlight light exposure as a potentially modifiable, non-invasive target for behavioral interventions aimed at improving the quality of life in ME/CFS, representing a promising emerging for future translational research.
Few studies have described physiological and cardiac rhythm responses to maximal voluntary breath-holding in elite freedivers. This case study presents minute ventilation, PETO2, PETCO2, involuntary breathing movements (IBMs; surface electromyography), SpO2, muscle and cerebral oxygenation (near-infrared spectroscopy), and cardiac rhythm changes (electrocardiogram) before, during, and after a maximal dry static voluntary breath-hold in a world champion freediver. Glossopharyngeal insufflation prior to the breath-hold increased forced vital capacity from 6.92L (138% predicted) to 9.04L (180% predicted). Compared to resting end-tidal gas pressures, the breathe-up in preparation of the breath-hold increased PETO2 (108mmHg to 135mmHg) and decreased PETCO2 (36mmHg to 21mmHg). The breath-hold was 06'07" in duration, of which 02'20" was spent in the easy-going phase and 03'47" in the struggle phase - the latter encompassing a total of 48 IBMs. Throughout the breath-hold, PETO2 decreased to 38mmHg and PETCO2 increased to 65mmHg. SpO2 decreased from 97% to 73%. Muscle oxygenation decreased from 50% to 22%, whereas cerebral oxygenation remained relatively stable until the final ∼20s of the breath-hold (∼68% to ∼62%). Heart rate variability-based markers of autonomic cardiac activity decreased during the easy-going phase, increased during the struggle phase, and normalized after. Asymptomatic bradycardia with competition between sinus bradycardia and junctional rhythm and (supra)ventricular extrasystoles manifested throughout the struggle phase and resolved after breath-hold cessation. This report of a world champion freediver shows that a long voluntary breath-hold induced transient asymptomatic cardiac arrhythmias, likely linked to the physiological stress of extreme voluntary breath-holding.
Rhythmic sniffing is considered intrinsic to active olfaction among terrestrial mammals. However, mice are known to briefly hold food under their nares while feeding, suggesting coordination of oromanual dexterity, breathing, and olfaction for nonrhythmic single sniffs. Here, we recorded kinematics and breathing as mice foraged and fed, finding that mice indeed, with clockwork-like dexterity and millisecond timing, synchronize a single inspiration with rapid head and hand movements. These solitary food sniffs are associated with abrupt resetting of the breathing rhythm, differ from stereotypical rhythmic sniffing, and exhibit behavioral modulations for different food properties. Olfactory and motor circuit manipulations demonstrate motor cortical dependence rather than reflexive neural control. Our study extends the concept of active olfaction to include this distinct form of complex motor-sensory coordination, features of which accord with the idea of discrete "snapshot" olfaction.
Neurodivergent neurotypes refer to brains that function differently from what is considered the societal standard or "stereotypical" norm, and include autism and attention deficit hyperactivity disorder (ADHD). Currently, global estimates suggest over 15% to 20% of the global population is neurodivergent. Autistic people and those with ADHD often experience mental health problems and have a heightened likelihood of anxiety and depression. Epidemiological evidence shows that sleep and circadian rhythm disruption, such as low self-reported sleep quality, insomnia symptoms, and delayed sleep-wake phase disorder, are common in autistic people and in those with ADHD. Despite scientific advancements, a comprehensive framework integrating sleep and circadian factors associated with mental health problems in neurodivergent neurotypes remains currently undeveloped. This perspective, written by people with lived experience of neurodivergent neurotypes, examines mental health problems, particularly anxiety, depression, and suicide risk, in autistic people and those with ADHD; sleep and circadian rhythm disruption in these neurotypes; and the growing epidemiological evidence linking sleep, circadian, and mental health problems in these neurotypes compared to people with neurotypical development. Our perspective advocates for an integrated model that accounts for the interplay between sleep, circadian rhythms, and mental health in neurodivergent neurotypes. Moreover, it identifies gaps and future research avenues, and the need for personalized behavioural interventions to improve their sleep, circadian, and mental health problems. Co-production of research is advocated as a method to ensure that insights from neurodivergent neurotypes are included as equal partners in the entire research process, to best support their sleep, circadian, and mental health.
Recent multi-omics work shows that the diurnal rhythmicity of kidney function is associated with circadian oscillations in renal mRNA, protein and metabolite abundances. Yet circadian regulation of renal lncRNAs, which are emerging as important modulators of diverse (patho)physiological processes, remains largely unexplored. Here, we provide a comprehensive characterization of renal lncRNA expression across cell types and circadian time points using bulk RNA-Seq and single-nucleus RNA-Seq (snRNA-seq) using kidney samples from male mice. Although the majority of lncRNAs are lowly expressed and only a fraction are annotated, their profiles sufficed to distinguish nearly all renal cell types. Compared with mRNAs, lncRNAs were more cell-type specific and an inverse correlation between cell-type specificity and expression level was evident. To assess the role of the circadian clock, we used mice lacking the core-clock regulator BMAL1 in renal tubules. Approximately one-sixth of lncRNAs and one-third of mRNAs were rhythmic. In contrast with mRNAs, lncRNAs exhibited an asymmetric temporal distribution between night and day, with peak expression occurring preferentially during the inactive phase of the mice. Bmal1 deletion partially disrupted rhythmicity in both biotypes and altered overall expression levels; lncRNAs were predominantly upregulated. These findings uncover the diversity of renal lncRNAs, their cellular distribution and their circadian regulation in male mice.